Martin, et al., "Experimental Studies on the Prediction and Prevention of Stress Ulcers Using Tonometry, Reflectance Spectrophotometry and Oxygenated Perfluorochemicals," Japanese Journal of Surgery, Vol. 21, No. 6, page 661 (1991), have investigated whether oxygenated perfluorochemicals protect the gastric mucosa against hemorrhage-induced stress ulcerations. Prior to their work, it had been reported by others that a close correlation existed between the occurrence of stress ulcers and the degree of gastric mucosal ischemia resulting in a decreased intramural pH. Using a dog model, Martin, et al. treated one group by lavaging the stomach with a modified Fluosol.RTM.-DA 20% emulsion. Fluosol.RTM.-DA was obtained from The Green Cross Corporation, Osaka, Japan, and contains the oxygen-transporting perfluoro-chemicals perfluorodecalin and perfluorotri-n-propylamine. The Fluosol.RTM.-DA emulsion was oxygenated by bubbling with 100% oxygen. Lavage was commenced when the gastric intramural pH decreased to 7.24 following hemorrhagic shock, which pH level was considered to be the critical level of ischemia, and was terminated just before reinfusion of the shed blood. Martin, et al. describe their results as indicating that local application of Fluosol.RTM.-DA can increase tissue oxygen saturation of the stomach during shock and can also protect the mucosa against acute ulceration. The severity of macroscopic gastric mucosal lesions in the oxygenated Fluosol.RTM.-DA treated group was stated to be significantly less than that of two control groups.
The method of Martin, et al., although potentially offering therapeutic benefit, is impractical. The preparation of oxygen-containing emulsions is a labor-intensive endeavor. Thus far, there has not been a truly cost-effective method by which existing oxygen carrying emulsions could be used to practice the method of Martin, et al. Although the practitioner might then theorize the use of neat perfluorochemical liquids in the process of Martin, et al., there are possible problems with the administration of neat perfluorochemicals to the mammalian gastrointestinal tract. In both the gastrointestinal tract and peritoneal cavity, there is the potential for introduction of the neat perfluoro-chemical into the vascular system through the presence of large or small ulcerations or abrasions or other connection between the gastrointestinal tract or the peritoneal cavity and the vascular system. The safety of neat perfluorochemical introduced into the vascular system cannot be presumed. Further, the long term exposure of internal body cells to neat perfluorochemicals has not been established.
Polymeric balloons or bags inflated with saline have been tried as intragastric devices to aid in weight reduction for obese patients. Latex balloons failed within a few weeks, while silicone elastomer balloons maintained their volume for one year and longer. See McFarland, et al., "The intragastric balloon: a novel idea proved ineffective," British Journal of Surgery, Vol. 74, No. 2, page 137 (1987). McFarland, et al. describe a method for inserting into the stomach an empty balloon with a connected fill tube through which liquid can be passed into the balloon. Once the balloon reached the stomach under fluoroscopic guidance, Conray 280 (May and Baker) was inserted into the balloon through the fill tube for clear identification.
Fluosol.RTM.-DA is now commercially available to the medical profession in the United States from Alpha Therapeutic Corporation of Los Angeles, Calif., and is supplied in a plastic bag which is gas permeable, but impermeable to most liquids. Indeed, Fluosol.RTM.-DA is not supplied oxygenated because oxygen in the bag could diffuse out through the plastic bag and nitrogen or other gas in the air could diffuse into the plastic bag to reach equilibrium. Such a bag is a MEDIDEX brand bag provided by Nariwa Rubber Company, Nara, Japan, formed of a polyvinyl chloride containing a polyester polyurethane plasticizer as described in U.S. Pat. No. 3,940,802.
U.S. Pat. No. 4,963,130 by Osterholm describes the intra-peritoneal perfusion of an oxygenated fluorocarbon as an artificial lung. In this instance, the oxygenated fluorocarbon liquid is circulated through the peritoneal cavity for general body oxygenation. Osterholm recognizes certain disadvantages in the practice of this method, noting that steps may need to be taken to minimize the incidence of peritoneal infection, and that the neat fluorocarbon is not preferred because, following completion of treatment, a lavage should be administered to wash remaining fluorocarbon from the peritoneum.
Similarly, Faithful, et al., "Whole Body Oxygenation Using Intraperitoneal Perfusion of Fluorocarbons," B. J. Anaesth., 56, page 867 (1984), continuously pumped oxygenated Fluosol.RTM.-DA emulsion into the peritoneal cavities of rabbits and reported that extra pulmonary oxygenation using peritoneal lavage was feasible. However, the authors noted potential problems with the whole body approach, namely, the question of possible oxygen toxicity of the peritoneal surfaces and degree of absorption of the fluorocarbons, possibly leading to hepatic toxicity. Thus, another problem in utilizing perfluorocarbons as oxygen-transporting systems within the cavities of the body is to develop a means in which to control the amount of oxygen discharged over time from the fluorochemical for availability by the body.